Identification of hub genes and potential molecular mechanisms related to radiotherapy sensitivity in rectal cancer based on multiple datasets.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36879254", "kind": "science-record", "revision": 3, "content_hash": "sha256:e62a86f16c0086c3ef9792be9069079f15d2546635d30069f5b9188150f7a0bf", "created_at": "2026-11-01T19:01:30Z", "updated_at": "2026-11-01T22:09:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes and potential molecular mechanisms related to radiotherapy sensitivity in rectal cancer based on multiple datasets.", "doi": "10.1186/s12967-023-04029-2", "pmid": "36879254", "authors": ["Pengfei Zhao", "Hongchao Zhen", "Hong Zhao", "Yongjie Huang", "Bangwei Cao"], "journal": "Journal of translational medicine", "year": 2023, "abstract": "BACKGROUND: Radiotherapy resistance is the main cause of low tumor regression for locally advanced rectum adenocarcinoma (READ). The biomarkers correlated to radiotherapy sensitivity and potential molecular mechanisms have not been completely elucidated.\nMETHODS: A mRNA expression profile and a gene expression dataset of READ (GSE35452) were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) between radiotherapy responder and non-responder of READ were screened out. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for DEGs were performed. Random survival forest analysis was used to identified hub genes by randomForestSRC package. Based on CIBERSORT algorithm, Genomics of Drug Sensitivity in Cancer (GDSC) database, Gene set variation analysis (GSVA), enrichment analysis (GSEA), nomogram, motif enrichment and non-coding RNA network analyses, the associations between hub genes and immune cell infiltration, drug sensitivity, specific signaling pathways, prognosis prediction and TF - miRNA regulatory and ceRNA network were investigated. The expressions of hub genes in clinical samples were displayed with the online Human Protein Atlas (HPA).\nRESULTS: In total, 544 up-regulated and 575 down-regulated DEGs in READ were enrolled. Among that, three hubs including PLAGL2, ZNF337 and ALG10 were identified. These three hub genes were significantly associated with tumor immune infiltration, different immune-related genes and sensitivity of chemotherapeutic drugs. Also, they were correlated with the expression of various disease-related genes. In addition, GSVA and GSEA analysis revealed that different expression levels of PLAGL2, ZNF337 and ALG10 affected various signaling pathways related to disease progression. A nomogram and calibration curves based on three hub genes showed excellent prognosis predictive performance. And then, a regulatory network of transcription factor (ZBTB6) - mRNA (PLAGL2) and a ceRNA network of miRNA (has-miR-133b) - lncRNA were established. Finally, the results from HPA online database demonstrated the protein expression levels of PLAGL2, ZNF337 and ALG10 varied widely in READ patients.\nCONCLUSION: These findings indicated that up-regulation of PLAGL2, ZNF337 and ALG10 in READ associated with radiotherapy response and involved in multiple process of cellular biology in tumor. They might be potential predictive biomarkers for radiotherapy sensitivity and prognosis for READ.", "claims": [{"id": "claim-method", "statement": "We used a random survival forest algorithm to rank the importance of prognostic related genes (nrep = 1000, which indicated that the number of iterations in the Monte Carlo simulation was 1000).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36879254", "locator": "sections[5] \"Identification of hub genes by random survival forest analysis\" paragraph 2", "quote": "We used a random survival forest algorithm to rank the importance of prognostic related genes (nrep = 1000, which indicated that the number of iterations in the Monte Carlo simulation was 1000)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The data that support the results of current study is available on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) websites.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36879254", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The data that support the results of current study is available on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) websites."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PLAGL2, ZNF337 and ALG10 were identified as three hub genes associated with radiotherapy response and prognosis in READ.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36879254", "locator": "sections[16] \"Random survival forest analysis of DEGs and identification of three hub genes of PLAGL2, ZNF337 and ALG10\" paragraph 2", "quote": "Among these eight genes, only three hub genes had statistical significance by Kaplan-Meier survival analysis, which were PLAGL2, ZNF337 and ALG10 (Fig. 2C, D and E)."}, {"asset": "source:pmid:36879254", "locator": "sections[16] \"Random survival forest analysis of DEGs and identification of three hub genes of PLAGL2, ZNF337 and ALG10\" paragraph 2", "quote": "Moreover, the expression of the three genes was significant higher in radiotherapy responder READ patients than in non-responder patients (Fig. 2F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "PLAGL2, ZNF337 and ALG10 were identified as three hub genes associated with radiotherapy response and prognosis in READ.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36879254"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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